This invention is directed to a method of suppression of a progressive, inflammatory, autoimmune arthritis in a mammal, such as rheumatoid arthritis. Despite advances in treatment, arthritis remains an extremely serious health problem, particularly in view of the aging population in the United States and other developed countries, because arthritis is typically a disease of the elderly. Although rarely fatal, arthritis is a major cause of morbidity, loss of time from work, lost productivity and decrease in quality of life. It causes severe pair and loss of joint mobility and can make doing even simple tasks difficult.
Among the most serious forms of arthritis is rheumatoid arthritis. Rheumatoid arthritis is generally believed to be an autoimmune disease that is believed to be associated with activity of autoreactive T cells. It is believed that these cells cause the disease via a delayed-type hypersensitivity reaction. Although it is not completely certain which antigen these T cells recognize, one significant candidate is type II collagen. The possibility exists that other antigens may also play a role in the disease.
Substantial work has been done on genetic bases for susceptibility to the disease. This work has focused on MHC haplotypes. Thus, it may be possible to determine, from familial studies or direct genomic analysis, that some individuals are at particular risk for the development of rheumatoid arthritis.
Although a number of treatment methods and regimes exist for rheumatoid arthritis, none of them is as yet completely satisfactory. These treatment regimens include administration of non-steroidal anti-inflammatory drugs such as acetylsalicylic acid (aspirin), ibuprofen, naproxen, and other such agents, gold compounds, penicillamine, 4-aminoquinoline agents, and immunomodulators.
Collagen-induced arthritis (CIA) is a T-cell dependent animal model of rheumatoid arthritis (RA) (D. E. Trentham et al., "Autoimmunity to Type II Collagen: An Experimental Model of Arthritis," J. Exp. Med. 146: 857-868 (1977)). Within two weeks after immunization with type II collagen (CII) in IFA, susceptible rats develop polyarthritis with histologic changes of pannus formation and bone/cartilage erosion. In addition, humoral and cellular responses to CII occur in CIA as well as RA (E. Brahn, "Animal Models of Rheumatoid Arthritis: Clues to Etiology and Treatment" in Clinical Orthopedics and Related Research (B. Hahn, ed., Philadelphia, JB Lippincott Company, 1991). Consequently, CIA is a useful animal model of RA that serves as an in vivo system for the exploration of inflammatory synovitis etiologies and for the investigation of potentially new therapeutic interventions.
However, there exists a need for an improved treatment of rheumatoid arthritis and other autoimmune forms of arthritis that can suppress or ameliorate symptoms such as inflammation, swelling, abnormal neovascularization, bone erosion, or cartilage erosion. Preferably, such an improved method of treatment should be able to be combined with other treatment methods, should work rapidly to cause regression or stabilization of symptoms, and should be well tolerated. Preferably, such a treatment regimen should also be adaptable to prophylaxis in susceptible individuals.